Abstract P1-05-14: ctDNA IN BREAST MILK FOR EARLY DETECTION OF PREGNANCY ASSOCIATED BREAST CANCER
Authors: Cristina Saura, Carolina Ortiz, Enrique Javier Arenas, Judit Matito, Anna Suñol-Camas, Octavi Cordoba, Alex Martinez-Sabadell, Itziar Garcia-Ruiz, Ignacio Miranda, Clara Morales-Comas, Estela Carrasco Lopez, Cristina Viaplana, Vicente Peg, Paolo Nuciforo, Neus Bayo, Josep Maria Miquel, Marina Gomez-Rey, Guillermo Villacampa, Silvia Arevalo, Javier Carmona, Martín Espinosa-Bravo, Judith Balmaña, Rodrigo Dienstmann, Joaquin Arribas, Josep Tabernero, miriam sanso, Ana Vivancos
Journal: Cancer Research (2023)

Abstract The potential of cell-free tumor DNA (ctDNA) for early tumor detection in asymptomatic patients is yet to be established. In the case of pregnancy associated breast cancer (BC), early detection is of special interest, since it is an entity of special aggressiveness due to a delay in diagnosis, along with the negative effect of mammary gland involution when BC is diagnosed during the postpartum period (PPBC). Indeed, PPBC has double metastatic risk and worst prognosis. With a potential applicability for cancer screening during breastfeeding, here we explored the presence of ctDNA in breast milk (BM) from women with BC associated to pregnancy. Matched samples from breast tumor, plasma and BM from a cohort of 14 women diagnosed during pregnancy or breastfeeding were analysed by droplet digital PCR and a targeted next generation sequencing panel (NGS). Thirteen patients had early-stage disease (11% Stage I, 61% Stage II and 28% Stage III) whilst one was diagnosed at advanced stage. BM harboured ctDNA, since mutations present in the tumor tissue were detected in 86% of the cases by ddPCR and in 71,4% by NGS (difference owing to technique sensitivity). Matched plasma samples had detectable ctDNA levels in only 8% of the cases. In one of the patients, a BM sample collected 18 months prior to BC diagnosis revealed the presence of a pathogenic PIK3CA mutation later detected in the surgically removed tumor. With the ultimate goal of applying the NGS in BM as a technique for early detection of BC in the postpartum period, we have collected samples from healthy volunteers and patients at high risk of developing BC (defined as women becoming pregnant at &amp;gt;40 years or carriers of germ-line pathogenic variants associated with BC -ie: BRCA1, BRCA2, PALB2, RAD51C/D). The application of NGS in BM as a technique for early detection of BC in the postpartum period, identified in a high-risk woman (criteria of enrolment was the age, 46yo) an AKT1 pathogenic mutation in the right-sided BM anticipating by 6 months the radiological diagnosis of a Luminal A tumor, stage pT1bN0M0. In summary, our data provides evidence that ctDNA in BM is highly prevalent even at initial tumor stages, and could be exploited for early breast cancer screening during breastfeeding. Citation Format: Cristina Saura, Carolina Ortiz, Enrique Javier Arenas, Judit Matito, Anna Suñol-Camas, Octavi Cordoba, Alex Martinez-Sabadell, Itziar Garcia-Ruiz, Ignacio Miranda, Clara Morales-Comas, Estela Carrasco Lopez, Cristina Viaplana, Vicente Peg, Paolo Nuciforo, Neus Bayo, Josep Maria Miquel, Marina Gomez-Rey, Guillermo Villacampa, Silvia Arevalo, Javier Carmona, Martín Espinosa-Bravo, Judith Balmaña, Rodrigo Dienstmann, Joaquin Arribas, Josep Tabernero, miriam sanso, Ana Vivancos. ctDNA IN BREAST MILK FOR EARLY DETECTION OF PREGNANCY ASSOCIATED BREAST CANCER [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-14.